Synthesis of 1,5-Disubstituted 3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines

Summary. A series of 1,5-disubstituted 3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines were synthesized by the reaction of α,β-unsaturated ketones derived from dehydroacetic acid and hydrazine in hot acetic acid or propionic acid. The structures of all new compounds were elucidated by microanalyses, ¹H and ¹³C NMR, IR, and mass spectroscopic measurements.     

Synthetic and mechanistic aspects of α-alkylation and α-arylation of β-dicarbonyl compoundsvia their transition metal complexes

Some transition metal complexes of β-dicarbonyl compounds react with electrophiles at α-C. These reactions, carried out under neutral conditions, offer a broader scope than their conventional counterparts, and are generally performed in the presence of stoichiometric or catalytic amounts of strong bases. Mechanistic observations using different reaction conditions are also relevant from a synthetic point of view. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 418–427, March, 1997.     

Ionene-Bound Borohydrides: Efficient, Selective, and Versatile Polymer-Supported Reducing Agents

Summary. Reduction of structurally different carbonyl compounds, such as aldehydes, ketones, α,β-unsaturated enals and enones, acid chlorides, and imines was accomplished efficiently using high capacity ionene based borohydride reagents. Aldehydes and imines were reduced to the corresponding alcohols and amines in excellent yields in methanol at ambient temperature while ketones and acid chlorides were reduced in iso-propanol and THF-MeOH at reflux. Chemoselective reduction of aldehydes over ketones was achieved successfully with these reagents. Complete regioselectivity was also observed in the reduction of α,β-unsaturated aldehydes and ketones.     

Boron chelates in the synthesis of α,β-unsaturated ketones of the coumarin series

Condensation of aromatic aldehydes with 3(8)-acetyl-4(7)-difluoroboryloxycoumarin intramolecular complexes gave boron complexes of α,β-unsaturated ketones, whose hydrolysis afforded the corresponding hydroxy cinnamoylcoumarins. The boron complexes and their hydrolysis products intensely absorb and fluoresce in the visible region of the spectrum. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2144–2150, December, 2006.     

Stereoelectronic structure of α-bromoalkenyl trifluoromethyl ketones

The results of quantum-chemical calculations at the B3LYP/6-311G** level of theory showed that (Z)-α-bromo-β-arylalkenyl trifluoromethyl ketones are more stable than the corresponding E isomers by 4–5 kcal/mol. Relatively large positive charge on the olefinic β-carbon atom and strong polarization of the C=C bond in both Z-s-cis and Z-s-trans conformers makes bromoalkenyl trifluoromethyl ketones the most potent Michael acceptors among α,β-unsaturated carbonyl compounds. The calculated data are very consistent with the experimental IR spectra.     

Condensations of Ethyl 3-Ethoxy-4-(triphenylphosphoranylidene)-2-butenoate with α,β-Unsaturated Carbonyl Compounds

Summary.  Wittig condensations of α,β-unsaturated carbonyl compounds with ethyl 3-ethoxy-4-(triphenylphosphoranylidene)-2-butenoate gave good to high yields of (2E,4E,6E)-ethyl 3-ethoxy-2,4,6-alkatrienoates. Some of last mentioned compounds were almost quatitatively hydrolysed to (4E,6E)-ethyl 3-oxo-4,6-alkadienoates. This method can therefore be used as an attractive alternative for the preparation of unsaturated conjugated β-keto esters previously prepared in very low yields from α,β-unsaturated carbonyl compounds and ethyl 3-oxo-4-(triphenylphosphoranylidene)butanoate. Present address: Boron Molecular Pty. Ltd., PO Box 756, Noble Park, VIC 3174, Australia. E-mail: cmoorhoff@boronmolecular.com Received June 17, 2002; accepted June 21, 2002     

Polyfunctional fluoroalkyl-containing carbonyl compounds in the synthesis of heterocycles

Efficient procedures for the regioselective synthesis of fluoroalkyl-containing threefive-, six-, and seven-membered heterocycles as well as of related fused compounds, namely, α,β-epoxyketones, α,β-aziridinylketones, pyrazoles, pyrazolines, isoxazolines, 1,2-dithiolenes, amino- and mercaptopyrimidines, Δ^3,5-2-thioxo-1,3,2-thiazaphosphorines, Δ^3,5-2-thioxo-1,3,2-oxazaphosphorines, 2,3-dihydro-1,4-diazepines, azirino[1,2-a]quinoxalines, benzo[b]-and naphtho[2,3-b]-1,4-diazepines, and triazolopyridazines, which have been developed by the authors and coworkers, are summarized. The α- and β-functionalized fluoroalkylcontaining carbonyl compounds (β-diketones, β-ketoesters, their salts, regioisomeric β-aminovinyl ketones, β-aminovinylthiones, β-hydroxyketones, α,β-enones, and their halogen derivatives) were used as synthons in the processes of formation of the above-mentioned heterocycles. Dedicated to the memory of Academician I. Ya. Postovskii on his 100th birthday. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1279–1286, July, 1998.     

Concerning the Solvent Effect in the Aldol Condensation

Summary.  Except for the catalyst and the temperature, the nature of the solvent also affects the aldol condensation, favouring α,β-unsaturated carbonyl compounds in alcoholic solvents or β-hydroxyl carbonyl compounds in tetrahydrofuran. Received November 22, 1999. Accepted (revised) December 21, 1999     

Two-fragment α-adrenolytics

Dialkyl β-(2-aroxyethylamino)ethylphosphonates,N-[β-(2-methoxyphenoxy)ethyl]-N′-[β-(diethoxyphosphoryl)ethyl]-α,ω-diaminoalkanes, and diethyl β-(N-arylpiperazino)ethyl-phosphonates were synthesized by the reactions of dialkyl vinylphosphonates with β-aroxyethylamines,N-[β-(2-methoxyphenoxy)ethyl]-α,ω-diaminoalkanes, andN-aryl-piperazines, respectively. The compounds synthesized exhibit hypotensive and α-adrenolytic activities. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 987–991, May 1999.     

Condensations of Ethyl 3-Ethoxy-4-(triphenylphosphoranylidene)-2-butenoate with α,β-Unsaturated Carbonyl Compounds

 Wittig condensations of α,β-unsaturated carbonyl compounds with ethyl 3-ethoxy-4-(triphenylphosphoranylidene)-2-butenoate gave good to high yields of (2E,4E,6E)-ethyl 3-ethoxy-2,4,6-alkatrienoates. Some of last mentioned compounds were almost quatitatively hydrolysed to (4E,6E)-ethyl 3-oxo-4,6-alkadienoates. This method can therefore be used as an attractive alternative for the preparation of unsaturated conjugated β-keto esters previously prepared in very low yields from α,β-unsaturated carbonyl compounds and ethyl 3-oxo-4-(triphenylphosphoranylidene)butanoate.     

Regioselective phosphorylation of α-N-alkylamino ketones

General preparative methods for regioselective functionalization of α-amino ketones with organophosphorus reagents were developed. Stable phosphorylated derivatives of all their prototropic forms (α-amino ketones, α-hydroxy imines, and β-hydroxy enamines) were obtained for the first time. The relative thermodynamic stability sequence of α-amino ketones was found to be reversed upon their phosphorylation: O-substituted forms were more stable than N-substituted ones, in contrast to the equilibrium between the prototropic isomers. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 288—293, February, 2006.     

Use of X-ray diffraction data in stereochemical studies of (−)-menthone reactions with aromatic aldehydes

X-ray diffraction analysis proved that the stereochemical configuration of interaction products of (−)-menthone with aromatic aldehydes (α,β-unsaturated ketones or β-hydroxyketones) depends on the generation conditions of intermediate enolate carbanions. In irreversible deprotonation of (−)-menthone with strong sterically hindered organometallic bases, products of interaction with aldehydes preserve the 1R,4S-configuration; in equilibrium conditions, 1R,4R-diastereomers of the corresponding α,β-unsaturated ketones are formed with high stereoselectivity. Institute of Single Crystals, Academy of Sciences of Ukrainian Republic. Translated fromZhurnal Strukturnoi Khimii, Vol. 35, No. 5, pp. 133–142, September–October, 1994. Translated by T. Yudanova     

Synthesis of 1,5-Disubstituted 3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines

A series of 1,5-disubstituted 3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines were synthesized by the reaction of α,β-unsaturated ketones derived from dehydroacetic acid and hydrazine in hot acetic acid or propionic acid. The structures of all new compounds were elucidated by microanalyses, ¹H and ¹³C NMR, IR, and mass spectroscopic measurements.     

Spiro[4H-chromene-4,5′-isoxazolines] and related compounds: Synthesis and reactivities

Reactions of chromones with methyl ketoximes in the presence of lithium diisopropylamide follow the nucleophilic 1,2-addition mechanism to give spiro[4H-chromene-4,5′-isoxazolines] in good yields. The isoxazoline ring in spiro[4H-chromene-4,5′-isoxazolines] undergoes opening under the action of conc. H₂SO₄, yielding α,β-unsaturated oximes. Their nitrosation and bromination lead to the corresponding spiroisoxazolines, while the Beckmann rearrangement, to α,β-unsaturated amides. The latter are also formed directly from spiro[4H-chromene-4,5′-isoxazolines] under the action of PCl₅. N-Substituted acetophenone hydrazones in the presence of lithium diisopropylamide react at the C(4) atom of 2-trifluoromethylchromone, while acetophenone anil under the same conditions, at the C(2) atom. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 516–522, March, 2006.     

Formation of fluorosulfatodimerization products in reactions of perfluoroaliphatic α,β-unsaturated carbonyl compounds and conjugated dienes with electrochemically generated peroxydisulfuryldifluoride

Reactions of fluoroaliphatic α,β-unsaturated carbonyl compounds and perfluoro-2,7-dimethylocta-3,5-diene with electrochemically generated peroxydisulfuryldifluoride proceed to give both 1∶1 adducts and fluorosulfatodimerization products, whose formation is explained by generation of heteroallyl and allyl radicals due to the addition of a fluorosulfonyloxy radical to the sterically hindered vinyl carbon atom. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2207–2209, November, 1999.     

On the Reaction between 1-Aza-1,3-dienes and Push-Pull Olefins of the Acyloxymethylidene-malononitrile Type

Summary.  The reaction between push-pull olefins of the acyloxymethylidene-malononitrile type and α, β-unsaturated hydrazones affords selectively 5-alkyl-2-cyano-6-(N′,N′-dimethylhydrazono)-hexa-2,4-dienenitriles. No [4+2]-cycloaddition products were detected. The structure elucidation of the obtained compounds and possible reaction mechanisms are discussed. Received March 9, 2000. Accepted March 20, 2000     

Addition of hypobromous acid to 1-phenylcycloalkenes

Reaction of 1-phenylcyclooctene and 1-phenylcycloheptene with N-bromosuccinimide (NBS) in aqueous DMSO gives the corresponding 3-bromo-2-phenylcycloalkenes and 2-phenylcycloalk-2-enols in a ratio of 3 : 1. Unlike them, 1-phenylcyclohexene gives a mixture of 3-bromo-2-phenylcyclohexene and 2-bromo-l-phenylcyclohexanol. The oxidation of allylic alcohols with pyridinium chlorochromate afforded the corresponding α,β-unsaturated ketones.     

Synthesis of pseudo-C-nucleosides from β-formyl-α,β-unsaturated ester bearing a β-furanosidic moiety

Abstract  

Pseudo-C-nucleosides have potential biological activity, and an efficient synthesis of new pseudo-C-nucleosides has been developed via the reaction of a β-formyl-α,β-unsaturated ester bearing a β-sugar moiety with hydrazines in neutral and acidic conditions. The preparation of the β-formyl-α,β-unsaturated ester was accomplished by oxidation of the secondary hydroxyl group of 3-O-benzyl-1,2-O-isopropylidene-α-d-glucofuranose, followed by elongation of its carbon chain with (ethoxycarbonylmethylene)triphenylphosphorane and oxidation of the hydroxymethyl group.     

Mechanism for annelation ([2+4] cyclocondensation) of Schiff bases by β-dicarbonyl and β,β′-tricarbonyl compounds in amphiprotic media (review)

The mechanism was established for annelation ([2+4] cyclocondensation) of Schiff bases or azomethines by β-dicarbonyl and β,β′-tricarbonyl compounds in amphiprotic media. The condensation was found to be a self-catalyzed pericyclic process achieved through six-membered transition states. The key reaction intermediates are dipoles of quaternized azomethine ions and enol-anions of the β-dicarbonyl and β,β′-tricarbonyl compounds, which display 1,4-dipolarophilicity. Dedicated to Academician A. A. Akhrem of the Belarus Academy of Sciences on the Occasion of His Ninety-Fifth Birthday __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 335–346, March, 2008.     

Synthesis of spiro[indolo-1,5-benzodiazepines] from 3-acetyl coumarins for use as possible antianxiety agents

3-Acetyl coumarins (1) when allowed react with isatin (2) gave corresponding 3-(3′-hydroxy-2′-oxo indolo) acetyl coumarins (3), which on dehydration afforded the correspondingα,β-unsaturated ketones (4). Cyclocondensation of (4) with substitutedo-phenylene diamines resulted in novel 3-coumarinyl spiro[indolo-1,5-benzodiazepines] (5). Structures of all the compounds have been established on the basis of their IR, NMR and mass spectral data and have been screened for their antimicrobial activity and antianxiety activity in mice